Several non-invasive methods of imaging body organs have been developed over the past decades. These procedures are based on the tendency of a body organ to concentrate some detectable chemical. Particularly useful chemicals are those which emit gamma radiation. Subsequent scanning of the organ with a gamma ray camera provides an image of the organ from which diagnostic information can be obtained. .sup.99m Tc (Tc-99m) has been found to be particularly useful in this area because of its half-life and gamma ray emission.
Over the past several years different Tc-99m compounds have been disclosed for use as positive myocardial imaging agents. These different imaging agents, based on substantially different chemistries, have exhibited varying levels of utility in different mammals. To effectively image the heart the agent must localize in the heart and at the same time rapidly clear from neighboring organs such as the lungs and in particular the liver. Further, the imaging agent must not bind tightly to the blood or else image quality will be poor. An imaging agent which localizes in the heart and at the same time localizes in the liver does not provide a good image of the heart since the apex of the human heart is often obscured by the liver.
One recent patent which discloses Tc-99m myocardial imaging agents is Deutsch et al U.S. Pat. No. 4,795,626. This discloses a type of myocardial imaging agent which due to its ligand system is not reducible in vivo. Thus, the disclosed Tc(III) complexes remain in this oxidation state for imaging purposes. This has been found somewhat useful in myocardial imaging.
Unfortunately, the prototypical agent of this class has relatively slow blood clearance and high liver uptake which gives rise to rather low heart/liver ratio. This is reported in the Journal of Nuclear Medicine, 28:1070 1000, 1987. The ligand system acac.sub.2 en bonded to the four planar coordinations sites of the technetium and PMe.sub.3 (trimethylphosphine) bonded to the axial sites simply did not provide an efficacious myocardial imaging agent in humans.
One commercially acceptable product is Cardiolite sold by DuPont. This is an isonitrile Tc(I) complex. The isonitrile ligands contain alkyl ether groups. Also, Nuclear Medicine Communication, 10(4), April, 1989, p. 245 reports myocardial imaging agents in which .sup.99m Tc is complexed to bidentate phosphorus ligands containing alkyl ether groups. This brief abstract reports a heart/liver ratio of 0.75 which is lower than what is required to obtain a good myocardial image.